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Mi, Yu; Liu, Yutao; Feng, Si-Shen
Biomaterials, 06/2011, Letnik: 32, Številka: 16Journal Article
Abstract Although high efficacy has been showed, Paclitaxel and Docetaxel cause serious side effects due to the adjuvant used in their clinical formulation Taxol® and Taxotere® . We developed a micelle system with a newly synthesized TPGS2k polymer, which shows lower CMC of 0.0219 mg/ml compared with 0.2 mg/ml for traditional micelles with TPGS involved, to achieve sustained and controlled drug delivery with Docetaxel used as a model anti-cancer drug. The TPGS2k micelles were further conjugated to folic acid (FA) for targeted drug delivery. The Docetaxel-loaded TPGS2k micelles with and without FA conjugation were found of desired size and size distribution, high drug encapsulation efficiency and favorable drug release. In vitro studies using MCF-7 cancer cells demonstrated significantly the higher cellular uptake of the formulated drug for TPGS2k micelle formulation than that for Taxotere® . The targeting effects for the FA conjugated TPGS2k micelles are also demonstrated. The IC50 value, which is the drug concentration needed for 50% cell viability in the designated time period, is 103.4, 1.280 and 0.1480 μg/ml for MCF-7 cancer cells after 24, 48, and 72 h treatment respectively, which is greatly decreased to be 0.526, 0.251 and 0.233 μg/ml, i.e . a 99.5%, 80.4% decrease and 57.5% increase for the TPGS2k micelle formulation, and further decreased to be 0.1780, 0.1520 and 0.1140 μg/ml, i.e . a 99.8%, 88.1% and 23.0% decrease for the folic acid conjugated micelles, respectively. A synergistic effect between TPGS2k and Docetaxel is also achieved. The present work represents a new concept in the design of drug delivery systems – the carrier materials of the drug delivery system can also have therapeutic effects, which either modulate the side effects of, or promote a synergistic interaction with the formulated drug.
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